In the mammalian brain, dopamine systems are critical for the control of movement, hormone release, emotional balance and reward. Alteration of dopaminergic neurotransmission is involved in a variety of nervous system disorders. One such disorder is Parkinson's disease, which results from an intrastriatal deficiency in dopamine. Currently, there is no adequate method for treating or preventing the disease. L-DOPA has been administered to patients with Parkinson's disease, but such treatments are not generally considered to be effective.
Grafts of fetal neural tissue, such as mesencephalic tissue which contains dopaminergic neurons, have been shown to improve the symptoms of parkinsonism in humans and animal models. However, the use of such grafts has been limited, due in part to the difficulty in obtaining an adequate supply of transplant tissue. In addition, such tissue has not responded well to freezing, requiring the implantation of fresh tissue. In general, the use of fresh tissue is inconvenient and undesirable, since a period of time for evaluation of the tissue (e.g., to identify any viral contaminants) is beneficial.
Accordingly, there is a need in the art for stable mesencephalon cell lines that can be readily differentiated, and can be used as a renewable source of human mesencephalon dopaminergic neurons for Parkinson's research and drug discovery. The present invention fulfills these needs and further provides other related advantages.